Trends in Neurosciences

Toward a cross-species understanding of empathy.

Publication Date: 2013 Jun 7 PMID: 23746460
Authors: Panksepp, J. - Panksepp, J. B.
Journal: Trends Neurosci

Although signs of empathy have now been well documented in non-human primates, only during the past few years have systematic observations suggested that a primal form of empathy exists in rodents. Thus, the study of empathy in animals has started in earnest. Here we review recent studies indicating that rodents are able to share states of fear, and highlight how affective neuroscience approaches to the study of primary-process emotional systems can help to delineate how primal empathy is constituted in mammalian brains. Cross-species evolutionary approaches to understanding the neural circuitry of emotional 'contagion' or 'resonance' between nearby animals, together with the underlying neurochemistries, may help to clarify the origins of human empathy.

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Current insights into the C9orf72 repeat expansion diseases of the FTLD/ALS spectrum.

Publication Date: 2013 Jun 7 PMID: 23746459
Authors: Cruts, M. - Gijselinck, I. - Van Langenhove, T. - van der Zee, J. - Van Broeckhoven, C.
Journal: Trends Neurosci

An expanded G4C2 hexanucleotide repeat in the proximal regulatory region of C9orf72 is a frequent cause of neurodegenerative diseases in the frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND) spectrum. Although primarily characterized by variably abundant pathological inclusions of TDP-43 protein, the lesion load was extended to TDP-43-negative, p62-positive neuronal and glial inclusions in extended regions of the central nervous system (CNS), particularly in cerebellum, where they may be characteristic of a C9orf72 repeat expansion. Disease mechanisms associated with repeat expansion disorders, including haploinsufficiency, RNA toxicity, and abnormal translation of expanded repeat sequences, are beginning to emerge. We review genetic, clinical, and pathological highlights and discuss current insights into the biology of this novel type of repeat expansion disease.

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Interview with nancy kopell.

Publication Date: 2013 Jun PMID: 23731518
Authors:
Journal: Trends Neurosci

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Epigenetic layers and players underlying neurodevelopment.

Publication Date: 2013 May 31 PMID: 23731492
Authors: Lasalle, J. M. - Powell, W. T. - Yasui, D. H.
Journal: Trends Neurosci

Epigenetic mechanisms convey information above and beyond the sequence of DNA, so it is predicted that they are critical in the complex regulation of brain development and explain the long-lived effects of environmental cues on pre- and early post-natal brain development. Neurons have a complex epigenetic landscape that changes dynamically with transcriptional activity in early life. Here, we summarize progress in our understanding of the discrete layers of the dynamic methylome, chromatin proteome, noncoding RNAs, chromatin loops, and long-range interactions in neuronal development and maturation. Many neurodevelopmental disorders have genetic alterations in these epigenetic modifications or regulators, and these human genetics lessons have demonstrated the importance of these epigenetic players and the epigenetic layers that transcriptional events lay down in the early brain.

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Novel pathogenic pathways in diabetic neuropathy.

Publication Date: 2013 May 28 PMID: 23725712
Authors: Zenker, J. - Ziegler, D. - Chrast, R.
Journal: Trends Neurosci

Diabetic peripheral neuropathy (DPN) is a common complication affecting more than one third of diabetes mellitus (DM) patients. Although all cellular components participating in peripheral nerve function are exposed to and affected by the metabolic consequences of DM, nodal regions, areas of intense interactions between Schwann cells and axons, may be particularly sensitive to DM-induced alterations. Nodes are enriched in insulin receptors, glucose transporters, Na+ and K+ channels, and mitochondria, all implicated in the development and progression of DPN. Latest results particularly reinforce the idea that changes in ion-channel function and energy metabolism, both of which depend on axon-glia crosstalk, are among the important contributors to DPN. These insights provide a basis for new therapeutic approaches aimed at delaying or reversing DPN.

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Spikes and ribbon synapses in early vision.

Publication Date: 2013 May 21 PMID: 23706152
Authors: Baden, T. - Euler, T. - Weckstrom, M. - Lagnado, L.
Journal: Trends Neurosci

Image processing begins in the retina, where neurons respond with graded voltage changes that must be converted into spikes. This conversion from 'analog' to 'digital' coding is a fundamental transformation carried out by the visual system, but the mechanisms are still not well understood. Recent work demonstrates that, in vertebrates, graded-to-spiking conversion of the visual signal begins in the axonal system of bipolar cells (BCs), which transmit visual information through ribbon-type synapses specialized for responding to graded voltage signals. Here, we explore the evidence for and against the idea that ribbon synapses also transmit digital information. We then discuss the potential costs and benefits of digitization at different stages of visual pathways in vertebrates and invertebrates.

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Changing the tune: plasticity and adaptation of retrograde signals.

Publication Date: 2013 May 21 PMID: 23706151
Authors: Iremonger, K. J. - Wamsteeker Cusulin, J. I. - Bains, J. S.
Journal: Trends Neurosci

Retrograde signaling is a fundamental means by which neurons communicate. The acceptance of this statement has required a revision of how we view transmission and storage of information at the synapse. Although there is a substantial body of literature on the diverse molecules that serve as retrograde signals, less is known about how retrograde signal capacity can be modified. Is retrograde signaling plastic? How does this plasticity manifest? Are there behavioral correlates that may bias a neuron towards 'changing its tune', retrogradely speaking, of course? Here, we review recent findings that retrograde signaling is a highly labile process that adds additional layers of complexity that must be untangled to understand information processing in the nervous system.

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Where no synapses go: gatekeepers of circuit remodeling and synaptic strength.

Publication Date: 2013 Jun PMID: 23642707
Authors: Mironova, Y. A. - Giger, R. J.
Journal: Trends Neurosci

Growth inhibitory molecules in the adult mammalian central nervous system (CNS) have been implicated in the blocking of axonal sprouting and regeneration following injury. Prominent CNS regeneration inhibitors include Nogo-A, oligodendrocyte myelin glycoprotein (OMgp), and chondroitin sulfate proteoglycans (CSPGs), and a key question concerns their physiological role in the naive CNS. Emerging evidence suggests novel functions in dendrites and at synapses of glutamatergic neurons. CNS regeneration inhibitors target the neuronal actin cytoskeleton to regulate dendritic spine maturation, long-term synapse stability, and Hebbian forms of synaptic plasticity. This is accomplished in part by antagonizing plasticity-promoting signaling pathways activated by neurotrophic factors. Altered function of CNS regeneration inhibitors is associated with mental illness and loss of long-lasting memory, suggesting unexpected and novel physiological roles for these molecules in brain health.

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Emerging roles of metaplasticity in behaviour and disease.

Publication Date: 2013 Jun PMID: 23602195
Authors: Hulme, S. R. - Jones, O. D. - Abraham, W. C.
Journal: Trends Neurosci

Since its initial conceptualisation, metaplasticity has come to encompass a wide variety of phenomena and mechanisms, creating the important challenge of understanding how they contribute to network function and behaviour. Here, we present a framework for considering potential roles of metaplasticity across three domains of function. First, metaplasticity appears ideally placed to prepare for subsequent learning by either enhancing learning ability generally or by preparing neuronal networks to encode specific content. Second, metaplasticity can homeostatically regulate synaptic plasticity, and this likely has important behavioural consequences by stabilising synaptic weights while ensuring the ongoing availability of synaptic plasticity. Finally, we discuss emerging evidence that metaplasticity mechanisms may play a role in disease causally and may serve as a potential therapeutic target.

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How to erase memory traces of pain and fear.

Publication Date: 2013 Jun PMID: 23602194
Authors: Sandkuhler, J. - Lee, J.
Journal: Trends Neurosci

Pain and fear are both aversive experiences that strongly impact on behaviour and well being. They are considered protective when they lead to meaningful, adaptive behaviour such as the avoidance of situations that are potentially dangerous to the integrity of tissue (pain) or the individual (fear). Pain and fear may, however, become maladaptive if expressed under inappropriate conditions or at excessive intensities for extended durations. Currently emerging concepts of maladaptive pain and fear suggest that basic neuronal mechanisms of memory formation are relevant for the development of pathological forms of pain and fear. Thus, the processes of erasing memory traces of pain and fear may constitute promising targets for future therapies.

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Why size matters - balancing mitochondrial dynamics in Alzheimer's disease.

Publication Date: 2013 Jun PMID: 23582339
Authors: Duboff, B. - Feany, M. - Gotz, J.
Journal: Trends Neurosci

Once perceived as solitary structures, mitochondria are now recognized as highly dynamic, interconnected organelles. The tight control of their fusion and fission, a process termed 'mitochondrial dynamics', is crucial for neurons, given their unique architecture and special energy and calcium-buffering requirements at the synapse. Interestingly, in Alzheimer's disease (AD), a condition initiated at the synapse, mitochondrial dynamics are severely impaired. Of the two proteins implicated in AD pathogenesis, amyloid-beta (Abeta) and TAU, only the impact of Abeta on mitochondrial dynamics has been studied in detail. We highlight recent findings that TAU exerts a determinative effect in the regulation of mitochondrial dynamics, and therefore neuronal function. In this process, the GTPase DRP1 has emerged as a key target of both Abeta and TAU.

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Dissecting the diversity of midbrain dopamine neurons.

Publication Date: 2013 Jun PMID: 23582338
Authors: Roeper, J.
Journal: Trends Neurosci

Midbrain dopamine (DA) neurons are essential for controlling key functions of the brain, such as voluntary movement, reward processing, and working memory. The largest populations of midbrain DA neurons are localized in two neighboring nuclei, the substantia nigra (SN) and the ventral tegmental area (VTA). Regardless of their different axonal projections to subcortical and cortical targets, midbrain DA neurons have traditionally been regarded as a relatively homogeneous group of neurons, with a stereotypical set of intrinsic electrophysiological properties and in vivo pattern of activity. In this review, I highlight recent data supporting an unexpected degree of diversity among these midbrain DA neurons in the mammalian brain, ranging from their developmental lineages and different synaptic connectivity to their electrophysiological properties and behavioral functions.

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Neurons as targets for T cells in the nervous system.

Publication Date: 2013 Jun PMID: 23478065
Authors: Liblau, R. S. - Gonzalez-Dunia, D. - Wiendl, H. - Zipp, F.
Journal: Trends Neurosci

Accumulating evidence shows that T cells penetrate the central nervous system (CNS) parenchyma in several autoimmune, infectious, and degenerative neurological diseases. The structural and functional consequences for CNS neurons of their encounter with activated T cells have been investigated in several experimental systems, including ex vivo co-cultures, electrophysiology, and in vivo imaging. Here, we review the modalities of neuron/T cell interactions. We substantiate the contention that T cells are directly responsible for neuronal damage in a large number of neurological diseases and discuss mechanisms of neuronal damage mediated by distinct T cell subsets, the impact of which differs depending on the disease. Finally, we describe how a better understanding of the mechanisms at play offers new possibilities for therapeutic intervention.

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